Inhibition of the NorA efflux pump of Staphylococcus aureus by synthetic riparins

E. VERÇOSA DE M.; S.J. CHAVEZ GUTIERREZ ; J. PINTO DE SIQUEIRA JR.; R. MENDES DE FREITAS; F. ARAÚJO DE A.O.; W.J. PELÁEZ ; H.D. MELO COUTINHO; H. MEDEIROS BARRETO; L. MURATORI COSTA; J.H. LIMA FERREIRA; F.C. ALVES LIMA; G.W. KAATZ

JOURNAL OF APPLIED MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016 vol. 121 p. 1312 - 1322

1364-5072

Aim: The goal of this study was to increase knowledge about the antimicrobialactivity of some synthetic Riparin-derived compounds, alone or incombination with fluoroquinolone antibiotics, against a strain of Staphylococcusaureus resistant to fluoroquinolone by way of overexpression of the NorAefflux pump.Methods and Results: Microdilution tests showed that Riparins A and B didnot show any significant antibacterial activity against Staph. aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256 ug ml-1; Log P 2.95) < Riparin-C (MIC 102 ug ml-1; Log P 3.22) < Riparin-E (MIC 16 ug ml-1; Log P 3.57). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain.Riparin-B, which has two methoxyl groups at the phenethyl moiety, showedthe best modulatory effect. Conclusions: Riparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor.Significance and Impact of the Study: Our data suggest the possibility ofusing Riparin-B in combination with norfloxacin or ciprofloxacin for therapyof infections caused by multi-drug resistant Staph. aureus.